A Concise Route for the Synthesis of Pyranonaphthoquinone Derivatives

Abstract

An efficient synthesis of pyranonaphthoquinones is achieved by ethylenediamine diacetate-catalyzed reactions of 4-hydroxy-2-quinolones with a variety of a,b-unsaturated aldehydes in moderate yields. This method provides a rapid entry into biologically interesting a-lapachone derivatives with a variety of substituents on the pyran ring.

Syntheses of chromenes and chromanes via o‐quinone methide intermediates

“…By using pyridine as a catalyst and solvent, the product was formed in 54% yield. The best condition found was with ethylenediamine diacetate (10 mol %) as the catalyst in MeOH (75%) or benzene (80%) (Scheme ) [145]. As previously observed by Ferreira et al in 1980, only the dehydro‐α‐lapachones were formed under these reaction conditions (Scheme ).…”

Synthesis and Cytotoxicity Evaluation of a Series of 3-Alkenyl-2-Hydroxy1,4-Naphthoquinones Obtained by an Efficient Knoevenagel Condensation

“…The β-nor-lapachone (11a) was the most active compound in the MCF-7 tumor cell line. In general, the furan-(β-nor-lapachone) (11) derivatives were more active than pyran-β-lapachone (10), and the presence of the hydroxyl and acetate groups decreased the cytotoxicity of β-lapachone and β-nor-lapachone. Also the 2-(2-ethyl-but-1-enyl)-3-hydroxy- [1,4]naphthoquinone (4j) was shown to be the less cytotoxic for all tumor cell lines tested.…”

“…8,9 The high yield of 2-cyclopentylidenemethyl-3-hydroxy-1,4-naphthoquinone (4m, 94%) was obtained by the use of β-alanine/acetic acid in benzene under reflux, using only two equivalent excess of aldehyde, compared with five equivalent or higher used by Hooker. 4 Dehydropyranonaphthoquinones (6) could also be obtained using modified Knoevenagel procedure by one-pot condensation-cycloaddition using α,β-unsaturated aldehydes in the presence of ethylenediamine diacetate in moderate to good yields. 10 Anufriev et al, 11 in 1993, using a modified Hooker's methodology with methylamine hydrochloride in ethanol under reflux synthesized 3-alkenyl-2,5,8-trihydroxy-1,4-naphthoquinones (8) besides 3,3'-methylenebisnaphthazarine (9) from naphthopurpurin (7, Table 2). Using few aliphatic aldehydes (propionaldehyde, isobutyraldehyde and valeraldehyde), they observed mixtures of 8 and 9 and using acetaldehyde or paraformaldehyde just dimers were formed.…”

Efficient synthesis of tetrahydroquinolinones by acetic acid-mediated formal [3+3] cycloaddition

“…We previously developed new methodologies to prepare pyran derivatives from 1,3-dicarbonyls and a,b-unsaturated aldehydes using formal [3?3] cycloadditions catalyzed by indium(III) chloride or ethylenediamine diacetate (EDDA) as a key strategy (Scheme 1) [10][11][12]. Later, novel approaches were also designed by other groups using BF 3 ÁEt 2 O, TiCl 4 , and In(OTf) 3 Lewis acids as catalysts [13], phosphoric acids as Brønsted acid catalysts [14], and EDDA/ZnCl 2 as co-catalysts [15].…”